1. Field of the Invention
This invention relates to preparation of opiates such as 14-hydroxymorphinone, oxymorphone and naloxone from oripavine.
2. Background of the Invention and Related Art
Oxymorphone, a potent opiate analgesic, is a semi-synthetic substitute for morphine. It is about ten times as potent as morphine. In the United States, FDA has approved oxymorphone hydrochloride in oral, parenteral and suppository form. Naltrexone, methylnaltrexone, buprenorphine, nalmefene, nalorphine and naloxone are other useful opiates.
Oxymorphone can also be converted to these and other useful compounds, such as nal-compounds, including naloxone.
Oxymorphone is typically synthesized using thebaine, morphine or another compound as a starting material. Thebaine, when used, is generally obtained from the concentrated poppy straw (CSP-T), a poppy extract relatively rich in thebaine. Reaction schemes for producing oxymorphone from thebaine take several steps, to intermediates such as oxycodone, then conversion of the 3-methoxy group of oxycodone to the 3-hydroxy group of oxymorphone. U.S. Pat. No. 6,291,675, for example, discloses a method for O-demethylation of the 3-methoxy group of opiates by use of a lithium hydride compound, providing a yield of O-demethylated opioid of at least 23%. U.S. Pat. No. 5,922,876 discloses preparation of oxymorphone from morphine. The process includes protection of the 3-hydroxy group of morphine with an aceto or benzyl group.
Syntheses according to the present invention do not include the conversion of a 3-methoxy group present on opiates to a 3-hydroxy group, and are therefore expected to result in increased reaction efficiencies, such as reduced reaction complexities and increased yield.